Kind: captions
Language: en
the following is a conversation with
david sinclair he is a professor
in the department of genetics at harvard
and co-director
of the paul f glenn center for the
biology of aging
at harvard medical school he's the
author of the book lifespan
and co-founder of several biotech
companies he works on
turning age into an engineering problem
and solving it
driven by a vision of a world where
billions of people can live much longer
and much healthier lives quick mention
of our sponsors
on it clear national instruments
and i simply safe and lino'd
check them out in the description to
support this podcast
as a side note let me say that longevity
research challenges us to think
how science and engineering will change
society
imagine if you can live a hundred
thousand years even under controlled
conditions like in a spaceship say
then suddenly a trip to alpha centauri
that is uh 4.37 light years away
takes a single human lifespan and on the
psychological maybe even
philosophical level as the horizons of
death drifts farther into the distance
how will our search for meaning change
does meaning require
death or does it merely require struggle
reprogramming our biology will require
us to delve deeper
into understanding the human mind and
the robot mind
both of these efforts are as exciting of
a journey as i can imagine
this is the lex friedman podcast and
here is my conversation
with david sinclair i usually feel like
the
same person when i was 12 like when i
right now as i think about myself i feel
like exactly the same person
that i was when i was 12 and yet
um i am getting older both body and mind
and still feel like time hasn't passed
at all do you um
feel this tension in yourself that
you're the same person
and yet you're aging yeah i have this
tension that that i'm still
a kid but that helps in my career
scientists need to have a wonder about
the world and
you don't want to grow up 12 year olds
and even younger
i would say 6 7 year olds i've still got
that boy in me
and i can look at things it's a gift i
think that i can see things for the
first time if i choose to
and then explain them as i would to a 60
or 6 year old because i
i am that mentally but on the other hand
i'm getting older right
i run a lab of 20 people at harvard i've
got a book i've got
uh you know science to do companies to
run and so i have to
and on most days just pretend to be a
grown up and and be mature but i
definitely don't feel that way
there's uh there's something i really
appreciated in
opening your book you talked about your
grandmother
and on this kind of theme on this kind
of topic
uh she first of all had a big influence
on you
my grandma mother had a big influence on
me
he also mentioned this poem by the
author of winnie the pooh
allen alexander milne maybe i can
read it real quick because i on the
topic of being children
when i was one i had just begun when i
was two
i was nearly new when i was three i was
hardly me
when i was four i was not much more when
i was five
i was just alive but now i am six
i am as clever as clever so i think i'll
be six
now forever and ever
um so this idea of
being six and staying six forever
being youthful being curious being
childlike
this and other things what uh
influence has your grandmother had in
your thinking about
life about death about uh love
yeah i was getting misty-eyed as you
read that because that that poem was
read to me
very often if not every day by my
grandmother who partially raised me
and she was as much a bohemian as an
artist philosopher
and she's one of those people that
wouldn't talk about the little things
she said i hate small talk
don't talk to me about politics or the
weather yeah talk to me about
human beings and culture so i was raised
on that and
this poem was one that she read to me
often because she knew
that the mind of a child is precious
it's honest uh it's pure and she grew up
during the second world war and in
hungary and budapest
witnessed the worst of humanity she was
trying to save
a whole group of jewish friends in her
apartment
saw what happened after the world war
which was um
there was the the russians were in
control and
locals weren't necessarily treated well
if they were rebellious which she was
and then there was the revolution in 56
which she was part of and had to escape
the country so she saw what can happen
when humans
do their worst and her words to me
expressed in part through that poem was
david
always stay young and innocent and have
wonder about the world
and then do your best to make humanity
the best it can be
and that's who i am that's what i live
for that's what i get up in the morning
to do is to leave the world a better
place
and show to whoever's watching us
whether it's aliens or some future human
historian that we can do better than we
did in the 20th century
you know we mentioned offline this idea
of bringing people back to life
through um through artificial
intelligence
sort of i don't know if you've seen
videos of
basically animating people back to life
meaning uh whether it's for me
personally i've been working
on specifically about albert einstein
but also alan turing
isaac newton and richard feynman
and it's it's an opportunity to bring
people that meant a lot
to others in the world and uh
animate them and be able to have a
conversation with them
at first to try to visually
visually explore the the full richness
of character that they had
as they struggle with the ideas of the
modern age sort of it's less about
bringing back their mind and more
bringing back the
the visual quirks that made them who
they are
and then maybe in the future it's using
the textual the visual the the
the video the audio data to actually
compress
down the person for who they are and be
able to generate text there's a few
companies
there's replica which is a chat engine
that was born out of the idea of
bringing
the the founder uh lost her friend
uh to uh he he got ran over by a car
and the initial reason she founded the
company was
trying to just have a conversation with
her friend she trained
a machine learning uh natural language
system
on the text that they exchanged with
each other and try she had a
conversation with him
sort of after he was gone uh and it's
very
the the conversation was very trivial it
was obvious that it's
uh you know a ai agent but it
gave her solace it made her actually
feel really good
and that's the way i wonder if it's
possible to bring back
people that are that means something to
us personally not just einstein but
people that we've lost and in that way
achieve a kind of small artificial
immortality i don't know if you think
about this kind of stuff uh well i'd
definitely think about a lot of things
that that one's a really good one
there's a great black mirror episode
about the the wife who brings back the
the boyfriend or husband i think one of
the challenges with bringing back
richard feynman would be to
to capture his sense of humor but that
would be awesome um but yeah bringing
back loved ones would be great
especially if uh if it's
you're they're young and uh they die
early though it may hold you back from
moving on that's another
thing that could happen as a negative
but i think that's great and i also
think that it's going to be possible
especially when we're recording some of
us every aspect of our lives whether
it's
our face or uh things we see right
eventually one day everything we see can
be recorded and then you can
you can build somebody's experience and
and thoughts uh
speech and and you will have replicas of
everybody
um at least digitally and physically you
could do that too one day
but that that's a good idea especially
because there are people that i'd like
to meet
and i think it's easier than building a
time machine one person i'd love to meet
is benjamin franklin
really well i wouldn't go back in time
um i would but i'd prefer to bring him
into the future and say
can you believe we have this thinking
machine in our pockets now
and he just see the look on his face as
to where humanity has come because i
think of him as a modern guy
that just was before his time yeah so
you're you're thinking benjamin franklin
the scientist
not benjamin flanken the political thing
because he'd be very upset with congress
right now
right so maybe talk to him about science
and technology
not uh not politics or maybe just don't
get him on twitter because he'll be very
upset with human civilization
you know i wonder what their
personalities are like
isaac newton it does seem complicated to
figure out what their personality is
like
even friedrich nietzsche who i also
thought about feynman is
we just have enough video where we get
the full
kind of um i mean it shows you
how important it is to get not the
official
kind of book level presentation of a
human but the authentic
the full spectrum of humanity you
mentioned collecting data
about a person collecting the whole
thing the whole of life the ups and
downs the embarrassing stuff the
beautiful stuff
not just the things that's condensed
into a book and then with finding you
start to see that a little bit
through conversations you start to see
peaks of like that genius
and then through stories about him from
others
and then certainly you uh the sad thing
about alan turing for example
is there's very little if any
uh recording of him in fact i haven't
been able to find recording allegedly
there's supposed to be a recording of
him
doing some kind of radio broadcast but i
haven't been able to find anything
and so that that's that's that's truly
sad that it feels like it makes you
realize
how the upside how nice it is to collect
data
about a person uh to capture that person
there's that's the upside of the
modern internet age the digital age that
that information
uh yeah creates a kind of immortality
the and then you can choose to highlight
the best parts of the person maybe throw
away the
ugly parts and celebrate them even after
they're gone
so that's a really interesting
opportunity you um you've also mentioned
to me offline
that you're really excited about all the
different wearables and all the
different ways we can collect
information about our bodies about uh
well the whole thing is what's most
exciting to you
in terms of collecting the the
biological
uh data about a human being
well so i'm a biologist i find animals
and humans
as machines very interesting it's one of
the reasons i didn't become
an engineer or a surgeon i wanted to
understand how we actually are built
and so i think a lot about machines
merging with humans and the first of
that are the bio wearables
and so i talked a lot about this i wrote
about it um in life span the book and
pictured a future where you would be
monitored constantly
so that you wouldn't suddenly have a
heart attack you'd know that was coming
or you
you wouldn't go to the doctor and they
don't know if it's
you need an antibiotic or not um
long term how old are you how to fix
things what should you eat what should
you take what should you
do these devices i predicted would be
smarter
better educated than you than your
physician and would augment them
and then there'd be a human that would
just tick off to see if that it's
correct and they approve
i also was predicting in the book that
we would have video conferences with our
doctors and that medicines would be
delivered
initially by courier but eventually by
drones and get it to you sometimes in an
emergency
and that we could even have pills that
were synthesized or delivered
um in your kitchen and combined
certainly
what's amazing about that is that what
are we now
two years since the book came out even
less
and that future is basically here
already covered
uh 19 accelerates accelerated that
incredibly
so where we're at now in society is if
you if you want to pay for it you can
have a blood test that will detect
cancer 10 20 years earlier than it would
before it forms a tumor you can of
course do your genome very cheaply for
less than a hundred dollars now
there are bio wearables already i wear
this ring from aura
that i have number of years of data i've
been doing blood tests for the last 12
years with a company called inside
tracker which
i consult for and so i have all of that
data as well and there's
34 different parameters on my
testosterone my blood glucose my
inflammation and i use all that data to
of course i wear a watch that that
measure things as well i use that data
to keep my body in optimal shape so i'm
now 51
and according to those parameters i'm at
least as good as someone in their early
40s
and i if i really work at it i can get
my biochemistry down to
early to mid 30s though i like to you
know now
eat a little dessert once in a while
so that's the future we're in right now
anyone can do what i just said
but in the very near future just in the
next few years
you can be wearing wearables so i'm
currently wearing a little
what's called a bio sticker uh this one
i just put on last night uh it's about
an inch long a few millimeters yeah
people just listening it's
uh san diego's chest yeah it's just the
how does it attach it's just kind of
it sticks on sticks yeah so on one side
you have an on button that you press
the lights come on flashes four times
it's good to go it
immediately syncs to your phone and
this one uh the it's called a bio button
a nice name and there's a there's
another one that i have that i haven't
tried yet
that does ekg on your heart um this is
mainly for doctors to monitor patients
that go home after a heart attack or
surgery
but that's medical grade fda approved
device
so there will be a day in fact it's
already here that
doctors are using these to get patients
to go home and save
a week in hospital two thousand dollars
at least for each patient
that's massive safe um savings for the
hospital
but ultimately what i'm excited about is
a future that isn't that far off where
everybody certainly in developed
countries eventually these will cost a
few cents and rechargeable
the only cost will be the software
subscription that can be monitored
constantly
and to give an idea what this is
measuring me at a thousand times a
second
is my vibrations as i speak
my orientation it can already has told
me this morning how i slept
where i slept what side i slept on
uh we've got sneezing coughing body
temperature
heart rate heart of other parameters of
the heart
that would indicate heart health
these these data are being used to now
to predict sickness so
eventually we'll have just in the next
year or so the ability to predict
whether something or diagnose whether
something is pneumonia
or just a rhinovirus that can be treated
or not
right this is really going to not just
revolutionize medicine but i think
extend lives dramatically
because if i have if i'm going to have a
heart attack next week and that's
possible
this device should know that and i'll be
in hospital before i even have it
maybe you can talk a little bit about
inside tracker because i saw that
there's some really cool things in there
like it
actually so maybe you can talk about i
guess that you're collecting blood
and to give it the data so
and it has like basic recommendations on
how to improve your life
so we're not just talking about diseases
right like anticipating
having a particular disease but it's
almost like guiding your trajectory to
life how to
whether it's extend your your life or
just
live a more fulfilling like improve the
quality of life i suppose this is the
right way to say it
what how does inside tracker work uh
what the heck is it because i thought
there was also pretty cool
yeah what is it is it something other
people can use
you can definitely use it uh you can
sign up it's consumer
it's like a company consumer facebook
company it is yes
uh and i also want to democratize the
ability to
to just take a mouth swab eventually we
don't need to have a blood test
necessarily
but for now it's a blood test and and
you'd go to a lab core request in the
u.s
it's also available overseas you can
upload your own data
for a minimal cost and get the
algorithms the ai
in the background to take that data plot
where you are against others in your age
group as in terms of health and
longevity by your age they call it no
inner age but also
it provides recommendations and this
isn't just a bunch of bs it sounds like
it might be
to say i'll go eat this or go to that
restaurant and order that but it's
actually based on
they basically this company has entered
hundreds
now it would be thousands of scientific
papers into their database
and hundreds of thousands of human data
points and they have
tens of thousands of individuals that
have been tracked over time
and anonymously that data is used to say
what works and what doesn't
if you eat that what works if you take
that supplement what works
and i was a co-author on a paper that
showed that the recommendations for
food and supplements um
was better than the leading drug for
type 2 diabetes
that's so cool the idea that you can
connect like skipping
the human having to do this work you can
connect the scientific papers
almost like meta-analysis of the science
connected to the individual data
and then based on that sort of connect
your data to
whatever the proper group is within the
whatever the scientific paper is
to make the suggestion of how how like
how that work
applies to your life and then that
ultimately maps to like a recommendation
what you should do with your life
like it all like this giant system
that ultimately recommends you should
drink more coffee or less
right and and we'll have the genome in
there as well you can upload that yeah
uh and so so these programs will know us
way better than
we do and and our doctors as well the
idea of going to a doctor once a year
for an
annual checkup and having you know males
get a finger up their butt and
uh you know you cough that that to me is
a joke that's medieval
medicine and that's very soon going to
be seen as medieval
yeah it's um to me as a computer science
person
it's always upsetting to go to the
doctor and just
look at him and like realize you know
nothing about me
like you you're you're you're making
your like opinions
based on like it is very valuable
years of intuition building about basic
symptoms but you're just like it is
medieval
they're very good at it in fact doctors
in medieval times are probably
damn good at working with very little
but the thing is i'd rather pref
for a doctor that doesn't really know
what they're doing but has a huge amount
of data to work with
well you're right and many of my good
friends are doctors i work at hard
so i'm not against the profession at all
yeah but i think that
they need just as much help as anyone
else does
we wouldn't drive a car without a
dashboard we wouldn't think of it so why
would doctors do the same
if we could we step back to the big
profound philosophical
both tragic and beautiful question about
age
how and why do we age is it uh
from an engineering perspective he said
you like the biological machine
is that a feature or a bug of the
biological machine
it is both a bug and a feature uh
evolutionary speaking we
only live as long as we need to to
replace ourselves efficiently
if you're a mouse you're only going to
live two and a half years three years
you're probably going to die of
starvation predation freezing
in the winter so they they divert most
of their resources to reproducing
rapidly but they don't put a lot of
energy into preserving their soma which
is their body
conversely a baleen type of whale a
bowhead whale in particular will live
hundreds of years
because they're at the top of the food
chain and they can live as long as they
want
so they breed slowly and build a body
that lasts we're somewhere in between
because we've you know we've really only
just come out of the savannas where we
could be picked off by
a cat we were pretty wimpy going back
six million years ago
uh so we we actually need to evolve
quicker than evolution will and that's
why we can use our
oversized brains and intuition to give
us what evolution
not only didn't give us but took away
from us you know we're pathetic look at
our bodies
these arms if any of us even the
strongest person in the world went in a
cage with a chimpanzee
the chimp could knock that person's head
off no question so we're pathetic so we
need to engineer ourselves to be
healthier and longer lived
so getting to aging we we can do better
right whales do way better we're trying
to learn how whales do that
and if you ask really anybody in the
field now
professor they'll say there are eight or
nine
hallmarks of aging which are really it's
a it's a
word for causes of aging so that you
probably
have heard of some of these your
listeners will have a loss of telomeres
the ends of the chromosomes like their
little
ends of um shoelaces that kind of thing
they get too short cells stop dividing
becomes senescent
they they become they put out what are
called mitogens that cause cancer and
inflamma inflammatory molecules that's
another aspect of aging
cellular senescence another one is loss
of the energetic so mitochondria the
battery packs
wind down there's a whole bunch stem
cells
proteostasis well these are our achilles
heels that i'm talking about
that are common amongst all life forms
really
but if you wanted me to jump to the
chase as to where
what is the upstream defining factor if
we boil it down
what do we get so most biologists would
say you can't boil it down
it's too complex i would say you can
boil it down to an equation
which is the preservation of information
and lost due to entropy
i.e noise and that is the basis of my
research
it originally came out of discoveries in
yeast cells where
i went to mit in the 1990s you studied
bread
i kind of did i studied the uh the
makers of bread a little yeast called
saccharomyces cerevisiae which at the
time was
one of the hottest excuse the pun uh
organisms to work on yes
but they we we figured out in the lab
why yeast cells get old
and found genes that control that
process and made them live longer
which was an amazing four years of my
life
one of those genes had a name with an
acronym
sir2 now the two is irrelevant
the s-i-r is important and the most
important letter out of all of those
three is
i which stands for information silent
information regulator number two
when you put more copies of that gene in
just put in one more copy
the yeast cells lived 30 longer and
suppressed the cause of aging which was
the dysregulation of information in the
cell
and then so fast forward to now i've
been looking
in humans and mice because they live
shorter and
cheaper to study where the loss of
information
in our bodies is a root cause of aging
and i think it is your boldness
in viewing biology in this way is
fascinating
because that also leads to a kind of
uh it's almost like allows for a theory
of aging like like you could boil it
down to a single equation
and it leads to a perhaps a metric that
allows you to optimize
aging sort of in the fight against
entropy
to figure out which mechanisms like you
said the the silent information
regulator which mechanisms allow you to
preserve information
now without like without injecting noise
without
without creating entropy without
creating degradation of that information
for some reason converting biology
which i thought was mostly impossible
into an engineering problem
feels like it makes it amenable to
optimization
to solving problems to creating
technology that can
whether that's genetic engineering or ai
it makes it uh possible to uh
create the technology that would improve
the
the degradation of information and aging
is there more concrete ways you think
about the kind of information we want to
preserve
and also is there good ideas about
regulators of that information about
ways to
prevent the distortion and degradation
of that information
right so that we have some information
regulated genes in our bodies we have
seven of them
uh certain one through seven they're
called and we found in in mice
one way to slow down the loss of
information is to just give more of
these
um to up regulate these genes so we we
made a mouse that has more of this so t1
gene
turned it on and that slowed down the
aging of the brain
and preserved their information now what
information am i talking about you might
ask
well again you can simplify biology
there are two types of
information in the cell primarily the
one we all
read about and know about is the dna the
genome and that's
base four information atcg the four
chemicals that make up the various
sequences of the genome billions of
letters
and that also degrades over time but
what's been fascinating
is that we find that that information is
pretty much intact
in old animals and people you can clone
a dog one of my friends in l.a just
cloned his dog three times
so this is doable right it means that
the genome can be intact but
what's the other type of information
it's the epigenome
the regulators of the genetic
information
and physically that's really just how
the dna is wrapped up
or looped out for the cell to access it
and read it
so it's similar to an excuse this
analogy
but it's a good one um a compact disc or
a dvd
those pits in the foil are the digital
information that's the genome
and the epigenome is the reader of that
information and in
in a different cell you'd read different
music different songs
different symphonies and that's what
gets laid down when we're
in the womb and that gives makes a skin
skin cell forever a skin cell and not a
brain cell tomorrow
thank god otherwise our brains wouldn't
work very well but over time what we see
is
that the brain cells start to look more
like skin cells and the kidney cells
start to look more like liver cells
and they what we call x differentiate
this is a term that we use in my lab but
isn't yet widely used but we needed a
term to explain this and that those
that process of x differentiation the
loss of the reader
of the the cd or the dvd
we liken that to scratches
on the dvd so that the reader cannot
fully access the information
now we can slow down the scratches as i
mentioned we can turn on these genes we
can even put in
molecules into the cell or even eat them
and turn on those pathways which
which my father and i have been trying
to do for about a decade
to slow things down but the question
that i've had
is is there a repository of information
still in the body
because anyone who knows anything about
the loss of information or even has
tried to copy a cassette tape or
photocopy or xerox anything knows that
over time you you lose that information
irreparably
so i've been looking for a backup copy
inspired largely by claude shannon's
work
at mit as well in the 1940s
his theory mathematical theory of
communication is just brilliant and so
i've been looking for what he called the
observer
which is the backup copy we today might
call that the tcpi pro
tcp ip protocol of the internet that
stores information in case it doesn't
make it to your computer
it will fill in the gaps and we've been
spending
about the last five years to try and
find if there really is a backup copy in
the body
to reset the epigenome and polish those
scratches away
that's incredible so finding the backup
so whenever there are too many scratches
pile up
you can just write a new version
like right that not every new version
but go to the backup and restore it
right that's really all we're talking
about it's not that hard
once you know the trick and for people
that actually remember
uh like dvds and scratches on them how
frustrating it is
that that's a brilliant metaphor for
aging
and then the the reader is uh
is the thing that skips and then it
could destroy your experience
the richness of the experience that is
uh listening to your favorite song
right but in biology it's even worse
because you'll lose your memory your
kidneys will fail you'll
you'll get diabetes your heart will fail
and we call that aging
and age-related diseases so it's it most
people forget that
diseases that we get when we get old are
80 to 90
caused by aging and we've been trying to
fix things with band-aids after they
occur
without even generally talking about the
root cause of the problem
is there um the scratches
do those come from
are those programmed or are they
failures
meaning is it so if it's
by design then there's like a encoded
timeline schedule that the body's just
on purpose
degrading the whole thing and then
there's the just
the wear and tear of like the scratches
and a disc that happen
uh through time which which one is it
that's the source of aging
uh it's more akin to wear and tear there
isn't a program um getting back to
evolution
there's no selection for aging we're not
designed to age we just live as long as
we need to and then we're at the whim of
entropy basically second law of
thermodynamics
stuff falls apart we live a bit longer
than age 40
only because there are robust resilient
systems but eventually they fail as well
current limit to the human lifespan
where they completely fail is 122.
uh but so it's and i but i don't like to
think of it as wear and tear because
there's
there's two aspects to it there's a
system that's built to keep us alive
when we're young but actually ghost
comes back to bite us
as we get older and we call this this
issue
antagonistic pleiotropy what's good for
you when you're young
can cause problems when you're older
so we've been looking what what is the
cause of the main causes of the noise
and we've come we found two of them
definitively
the first one is broken chromosomes when
a chromosome breaks
the cell has to panic because that's
either going to cause a cancer or kill
the cell
there's only two outcomes it's pretty
much a problem uh and so what the cell
does is it
reorganizes the epigenome in a massive
way
what that leads to is think of it as a
tennis match or a ping pong
game the proteins are the bowls and they
now leave where they should be
which is regulating the genes that make
the cell type whatever it is
and they have to they have a dual
function they actually go to the break
the chromosome will break and fix that
and then they come back you might ask
well why is it set up that way well it's
a beautiful system it coordinates gene
expression
the control systems with the repair you
want them coordinated
problem is as we get older this ping
pong game some of the balls get lost
they don't come back to where they
originally started
uh and that's what we think is the main
noise
for aging and we've also the other cause
of aging that we found is is cell stress
we damage nerves
and they age rapidly so you that's the
other issue there's probably others
smoking chemicals for example we know
accelerates biological age pretty
dramatically
but the question is can you slow that
down or can you reset them to get those
ping-pong balls to go back to where they
originally started in the game
and we think we've found a way to do
that what can you give me hints
uh whose fault is it and the ball's not
coming back is it the proteins
themselves
like are they are they starting again
i've been obsessed with the protein
folding problem from the ai perspective
so
is it the proteins or is it something
else well we know who hits the balls
um and recruits them so that the brake
uh is recognized by proteins who send
out a signal
uh through phosphorylation is typical
way cells talk
to other proteins and that recruits
those
repair factors those ping-pong balls to
the brake so the cell's actively doing
this
to try and help itself but we don't know
who's to blame for them not coming back
um that could just be a flaw in the
quote-unquote design i don't think that
there's something saying
well one percent of you you bowls
proteins never go back
i just think it's hard to reset a system
that's constantly changing
we have in our bodies close to a
trillion dna breaks every day
and imagine that over 80 years what
damage that does to our epigenomic
information
now we know that this is well i should
we never know anything in biology but we
have strong evidence that this is true
because we can
mess with animals we can create dna
breaks
and tickle them with a few breaks maybe
raise it by threefold over background
levels of normal
breakage and if we're right those mice
should get old
and they do we can actually we've we've
created these breaks in a way that's
titratable we can it's like a rheostat
we can send it to 11.
you know i drove my tesla here i'm a big
fan of of
spinal tap two going to 11. if we go to
11 we can make a mouse old in a matter
of months
we prefer to go to a level of about four
and it gets old in 10 months
but it's definitely old it's got all of
the hallmarks of aging
it's got diseases it looks old its skin
is old it's got gray hair
but importantly we can now measure age
by looking at the scratches
we can look at the epigenome we can
measure it and use machine learning to
give us a number
and those mice are 50 older than normal
so you can replicate the aging process
in a controlled way you can all
i mean in a way that you i mean you
could accelerate it
in a controlled way and measure how much
exactly
it's aging and that gives you step one
of a two-step process to when you can
then figure out what how can we
reverse this and now we're reversing
those mice is there a good
i love what you said i mean in biology
you really don't know
it's it's such a beautiful mess uh
is is there is there ideas how to do
that is that on the
genetic engineering level is that uh
like what can you mess with
is it going to the trying to discover
the backup copies
and restoring from them like what's if
it's it's possible to convert it into
natural language words
what are the ideas here what is the
observer and how do we contact it
exactly what's the observer and how do
you contact or if there's other ideas
how to reverse the the the boss getting
lost process
yeah well you you can slow it down slow
it
but we found a reset switch recently we
just published this
in the december 2020 issue of nature
and what we found is that there are
three embryonic
genes that we could put into the adult
animal
to reset the age of the tissues and it
only takes four to eight weeks to work
well
and we can take a blind mouse that's
lost its vision due to aging
neurons aren't working well towards the
brain reset those neurons back to a
younger age
and now the mice can see again these
three genes
are famous actually because they're a
set of four genes
discovered by shinya yamanaka who won
the nobel prize in 2016
for discovering that those four genes
when turned on
at high levels in adult cells can
generate
stem cells and this is i think well
known now that we can create stem cells
from adult
tissue but what wasn't known is can you
partially take age back without becoming
a tumor
or generating a stem cell in the eye
which would be a disaster
and the answer is yes there is a system
in the body that can take the age of a
cell back to a certain point but no
further
safely and reset the age
and uh we're now using that to reset the
age of the brain of those mice that we
age prematurely
and they're getting their ability to
learn back
this is really exciting right like
what's uh what's the downside
of this well the downside is if you
overdo it and you don't get it right
uh you might cause tumors but we do
we do it very carefully and we also know
that in the eye it's very safe
yeah we also injected these we deliver
them by viruses so
we can control where and when they get
turned on
and in this paper we've published that
if we put high levels in the mouse
into their veins throughout the body
they don't get cancer for over a year
so i'm so optimistic that we're going
into human studies
in less than two years from now is there
a place where ai can help
sorry to inject one of the things i'm
very
excited about i'm passionate about so uh
deep uh google deep mind
recently had a big breakthrough with
alpha fold two but also half a fold
two years ago with um
achieving sort of uh state-of-the-art
performance on the protein folding
problem single protein folding
but it also paints a hopeful picture of
what's possible to do in terms of
simulating
the folding of proteins but also
simulating biological systems
through ai is there something to you
combined with this brilliant work on
the biology side that you're hopeful
about where ai can
be a tool to help where isn't that a
tool and if you're not using ai right
now in biology you're getting left
behind we use it all the time we're
using it to generate these
biological clocks to be able to read
those scratches
we're using it to predict the folding of
proteins so we can
target molecules and modulate their
activity we're using it to assemble
genomes of different species what else
we use it to predict the longevity of a
mouse based on how it reacts to certain
things
hearing eyesight generally frailty so we
have
we just put out a paper last year on
that um
the other thing we can use it for which
is a little off the track here but
we use it for predicting which
microorganisms are in your body
actually not predicting telling you so
our daughter natalie was infected with
lyme disease a few years ago
almost went blind from it and the test
took four days and i thought
just give me the dna for my spinal fluid
i'll go tell you what's in it if it's
lyme disease or not
they refused and so at that point i said
this has to be done better
so i've started a company that now can
take a sample of any
part of your body it's typically done
now with transplant
liver transplant patients to detect
viruses
that come out of their organs but that's
that's another area that ai is extremely
important for
um i i think if you're not in five years
if you're not using
you know deep learning you've got a
problem because the amount of data that
we generate now as biologists
is just terabytes can be terabytes per
week it'll eventually be terabytes per
day
and then we just go from there and i
actually have trouble recruiting enough
bioinformaticians a lot of our work is
now just number crunching
a part of that is collecting the data
which is kind of
something we've talked a little bit
about but is there something you can say
about how we can like can collect more
and more data
not just on the one person level
like for you to understand your like
various markers but to create
huge data sets to understand how we can
detect
certain pathogens detect certain
properties characteristics of
whether it's aging or all the other ways
the human body can fail
it seems like with the with biology
there's a kind of
privacy concerns that well actually not
privacy concerns it's almost like
regulation
that kind of prevents like hospitals and
sharing data
um you know i'm not sure exactly how to
say it but it
seems like when you look at autonomous
vehicles people are much more willing to
share data
when you look at human biology system
people are much less willing to share
data is there
a hopeful path forward where we can
share more and more data at a large
scale
that ultimately ends up helping us
understand the human body and then
treat problems with the human body so we
are right in the middle
we're living through what's going to be
seen as one of the biggest revolutions
in human health
through the gathering of data about our
bodies
and 20 years ago people didn't want to
go on social media they're worried about
it now
you have to if you're a kid that's for
sure
same with medical records these are
becoming all digitized and
and expanded ultimately we're going to
even if we don't want to have to be
monitored
there's going to be a court case that i
bet two three years from now someone's
going to say
how come my father died from a heart
attack you had these biosensors 20 bucks
and you didn't use it
lawsuit right there and suddenly all
hospitals have to
give you one of these there will be a
reversal like to where
it's your fault if you don't collect the
data that's brilliant
that's and that's absolutely right i
mean that's
absolutely right that's the frustration
i feel when going to the doctor
is like you're it's almost negligent
to not collect the data because you're
making if there's something really wrong
with me
and you're making decisions based on
very few tests
that's almost negligent when you have
the opportunity to collect a huge amount
more data
well like let me tell you something yeah
like the
i've got this inside tracker data for
for myself over a decade
and you'd think my doctor would roll his
eyes at this oh he's gone to a consumer
company blah blah blah
i had my first checkup in a year with
him through video conference
and he was running
blind he really didn't know what was
going on with me he asked the usual
things
how am i sleeping how am i eating these
kind of usual things
and i said well i've got new tests back
from inside tracker and he said
great i'd love to see them so i share
screen and we look at the graphs look at
the data
and he's loving it because he cannot
order these tests
willy-nilly so i said well let's order a
hba1c blood glucose levels because i'm
very interested in that that tracks with
longevity and he says well
i have no reason to order that do you
have a family history
no uh are you have any symptoms of
diabetes no well i can't order the test
i almost wanted to reach through the
computer and strangle him um
but instead you know i i pay a little
bit to get these tests done and then he
looks at them
so that's now the way consumer health is
going is that you can get better data
than your doctor can and but they like
you to do that
quick human question maybe you can
educate me
i've i think doctors sometimes have a
little bit of an ego
i understand that the doctor is super
experienced a lot of things but
this is a fundamental question of human
variability
like i know a lot of specific details
about like
um i mean depending of course what we're
talking about but there's a i bring a
lot of knowledge
and if i have data with me then i have
like
several orders of magnitude more
knowledge and i think there's an aspect
to where the doctor has to
put their expert hat like
take it off and actually be a curious
open-minded person and study
and look at that data do you think it's
possible to sort of
change the culture of the medical system
to where the doctors are almost
as you said are excited to see the data
or that's already happening it's really
happening now
we've probably lost the last generation
um that they're no hopers but
so i teach at harvard medical school and
they're excited about this
they're excited about aging which is a
new aspect to medicine
oh wow we can do something about that
and then yeah all this data what do we
do with it
there's still the traditional pathology
and all that stuff which they need to
know
but time will change their
their uh mindset i'm not worried about
that
and like we were discussing this isn't a
question of if it's just a matter of
when
and it's you know i have a front row
seat on all of this
i had breakfast with with the ceo who
uh is making this happen uh just
yesterday
i can tell you for sure that most people
have no idea that this revolution
is occurring and is happening so quickly
uh
if you're running a hospital and you can
save two thousand dollars per
cardiac patient what are you gonna do
you have to use it otherwise
you know the hospital down the road's
gonna be beating you
um and there are large hospital
aggregations so there's ascension and
others
that just have to go this way
for budgetary reasons and right now the
u.s spends what is 17 of their gdp
on healthcare for let's say one of these
buttons on my chest cost 20 bucks it's
rechargeable
and it can predict people's health and
save on antibiotics
prevent heart attacks how many billions
if not trillions of dollars
will that save over the next decade
yeah so when the public wakes up to this
they'll almost demand it
like this this should be this should be
accepted everywhere this is obvious
it's gonna save a lot of money it's
gonna improve the quality of life well
and the cfos of hospital
yeah groups will have to and insurance
companies are going to
want to get in on this so now that gets
to privacy right if
should an insurance company have access
to your data i would say
no but you could voluntarily show them
some of it if they give you a discount
and that's also being worked on right
now
i hope we do create kind of systems
where i can volunteer to share my data
and i can also
take the data back meaning like delete
the data request the deletion of data
and then maybe policy creates rules to
where
you can share data you could delete the
data
and i think if i have the option to
delete
all my data that that a particular
company has
then i'll share my data with everyone
like
i feel like uh if the if uh
because that gives me the tools to be a
consumer an
intelligent consumer of giving of
awarding my data to a company that
deserves it and taking it back when the
company is misbehaving
and in that way encourage as a consumer
in the capitalist system
encourage the companies that are doing
great work with that data
well yeah health care data security is
is number one
on on my mind uh inside tracker
made sure that that was true but you
know these
buttons on your chest there's very
private stuff they can probably tell
if you're having sex one night right so
this is not the kind of stuff you want
leaked
yeah so i don't know whether it's
blockchain or just for yourself i don't
want this public
life i guess it depends on how you how
how you go but yeah
uh you know there there's a lot of stuff
you don't want out there and
this definitely has to be number one
because it you know it's one thing to
have your credit card
information stolen it's another thing
health records are permanently out there
yeah so there's on the biology side
super exciting ways to um
to slow aging but there's also on the
lifestyle side
i've recently did a 72 hour fast it's
just an opportunity to take a pause and
be
you know appreciate life think about
like there's something about fasting
that um
encourages you to reflect deeper than
you otherwise might the time kind of
slows
and you also realize that you're human
because your body needs food and you
start to see your
is almost as a machine that that takes
food
and produces thoughts and then
and then ends briefly i mean there you
start to depending who you are
if you're like engineering minded you
start to think
of this whole thing as a kind of yeah as
a machine
and then also feelings fill this machine
uh feelings of gratitude of love but
also
the uglier things of jealousy and greed
and hate and all those kinds of things
you start to think okay how
how do i manage this body to create a
rich experience all that comes from
fasting for me
anyway but there's also health benefits
to fasting
i intermittent fast a lot i eat just one
meal a day
most of the time is there something you
can say about the benefits of fasting in
your own life
and in general the anti-aging process
well
you're a philosopher too sorry i
apologize no i'm impressed
uh through renaissance man uh it's it's
a joy to be here
uh so when it comes to fasting this is
you know being abstinence is one of the
the oldest ways to improve health right
probably they knew this 5000 plus years
ago
so that's not new but what we're
figuring out is what is optimal
and how does it work and one of the
things we helped contribute to
which i can speak to with some authority
is that these longevity genes we work on
we showed back in the early 2000s are
turned on by fasting
and at least in yeast we were the first
to show that how calorie restriction
fasting works to extend lifespan
that was the first for any species
something similar happens in our bodies
when we're hungry or put our bodies
under any other perceived adversity such
as running
our bodies think wow we're getting run
chased by a cyber
save tooth cat or something if we're
really hot or cold these probably also
work
to put our bodies in this defensive
state to activate these genes in the way
that whales do
and mice don't and so hunger is the best
way to do that
in fact i don't think you have to feel
hungry you can get used to it
but if there was one thing i would
recommend to anybody
to slow down aging would be to skip a
meal or two
a day now it doesn't mean you don't have
to live well you can go out i go to
restaurants i eat
regular food i try to be as healthy as
possible but i've gone from skipping
breakfast most of my life
now to skipping lunch as well and i have
my physique back that i had when i was
20. i feel
20 mentally i'm much sharper i don't
feel tired anymore i sleep well
so i'm a huge fan of the one meal a day
thing uh where i'm not good at is going
beyond
one day but have you ever fasted longer
than uh
than them 24 hours i tried doing two
days
i might have made it to the third and
given up i'm
i just find that i'm i'm not ver i don't
have a lot of willpower i also hate
exercise so
i'm not sure how long i'm going to live
but i've managed to do one meal a day so
if i can do that
seriously anybody can do that um to your
listeners and viewers i would say
don't try to do it all at once you can't
go from snacking
and eating three meals a day to what i
do easily
work your way up to it but also
compensate with drinking if you like tea
if you like coffee put some milk in it
um that's fine you can fill your stomach
up with with liquids
uh diet sodas i get criticized for
drinking but i'm going to continue to
have those
but then you know i power through the
day i definitely don't feel tired i
don't have a lag anymore but give also
give it at least two weeks because you
there's a habit as well having something
in your mouth chewing
feeling that fullness you can break that
habit and within two
three weeks you'll have done it
absolutely so i'm not actually even that
strict about it you said that soda
uh yeah people are very kind of weirdly
strict about fasting the rules and
the fasting like for example i i drank
uh element electrolytes when i was
fasting and that has like
five calories and so technically it's uh
not fasting or people will say like if
you drink coffee there's caffeine and
they'll say that's technically not
fasting because there's some kind of
biological effects of caffeine
whatever of course there's like
biological benefits that you can argue
about but there's also just experiential
benefits
just calorie restriction broadly has a
certain experience to it that
like for me personally just as you said
has made me feel really good
that said like especially uh i've gained
quite a bit of weight uh like maybe even
like 15 pounds something like that since
i moved to austin texas
and i i still keep the same diet but
i eat a lot of meat in that one
just because it's delicious because it's
also the
the the amazing people i met in texas
it's just there's like a camaraderie a
friendship of love to the people that
like makes you really enjoy
the uh the atmosphere of eating the
brisket and the meat is this joe rogan
insisting joe is i mean he's very
different
uh joe loves bread
and pasta like he knows that his body
feels
best doing keto or carnivore
so that's what he usually tries to stick
to
but he also does not hold back and he'll
just eat pasta when he does
pasta and he sort of enjoys life in that
way
i can't i don't know how to enjoy life
in that way i
also love pasta but i'm just not going
to enjoy it because i know
i i know my body ultimately does not
feel good with pasta so
it's a funny kind of dichotomies i i
would
like to uh cheat i guess by
eating more meat than i you know like
overeating uh on the things that
i know my body feels good on as opposed
to eating stuff i shouldn't like cake
and all those kinds of things
i tend to um i tend to find happiness in
overeating the good stuff versus
eating the bad stuff and the that's the
kind of balance
him he's like fuck it
every once in a while you got to enjoy
it and and then also coupled with that
for him
uh is just exercise like then faces
demons the next day and just
like burn a huge amount of calories
which is i mean
whatever whatever is up with that guy's
mind
there's an there's a ability to fully
experience life which is represented by
the pasta
and the ability to just like fight the
demons which is represented by all the
crazy kettlebells and
and running the hills and all this kind
of stuff that he does that takes a lot
out of you doing that kind of insane
exercise and
i think i'm more like you at least
towards your direction is like
i really hate exercise so i do it but i
really hate it
and so it's a balance that you have to
strike is there something you could say
about
the diet side of that for you personally
but in general in order to achieve
calorie restriction
like for me eating i know it may not
sound healthy but
eating carnivore eating mostly meat
has been has made me feel really good
both
mentally and physically is there
something you could say about the kinds
of diets
that may improve longevity but also
enable calorie restriction
well sure i mean the first thing that's
important to know is that
while many people are interested slash
obsessed with
what they eat the data that's come out
of animal studies at least
is it's far more important when you eat
than what you eat
and this was a fantastic study a few
years ago by
my friend rafael de cabo at the national
institutes of health in bethesda
and he had 10 000 mice on different
diets hoping to find the perfect mix of
carbs
protein and fat and it turns out that
the only ones that lived longer were the
ones that only ate
once a day and so that if we're we're
not mice but i think that we're close
enough to mice
that this tells us a lot but okay but i
still think the best bang for the
longevity buck is to do both well eat
less often and eat the right things now
i'll preface this to say
i'm not a nut about this i will eat
occasional
very occasionally a dessert usually i
steal from others which doesn't count
right
exactly but you've got to live life
right what's what's a long life if it's
not enjoyable anyway
but what i've i also found and this is
i'll get to your question a second but
my microbiome right now and stomach is
at a point where if i try to overeat
on a steak which i did a couple of days
ago i actually had a chicken
uh a fried chicken specifically
for two days i felt terrible i couldn't
sleep it wouldn't go down
so i'm now at a point where even if i
want to binge on meat and fried foods i
just can't it just feels bad
but what what do i recommend well what
the data says
which i try to follow is that
plant-based foods will
will be better than meat-based foods and
i know that there are a lot of people
disagree
but one of the facts is there's a few
facts one is that people who live a long
time tend to eat those type of diets
mediterranean okinawa
diet they're eating mostly plants with a
little bit of meat
and not a lot of red meat and the other
fact is that in
animals we know that there's a there's a
mechanism that's called
mtor little m capital tr that responds
to
certain amino acids that are found in
more abundance in meat
and when it responds it actually
shortens lifespan and the converse if
you starve it of those
three amino acids uh in mostly in meat
then it extends lifespan and there
there's a drug called rapamycin
which some people are experimenting with
that does that
so you might be able to you know i'm
just saying this here from
my colleagues we don't know the results
here but you could potentially take a
rapamycin-like drug
and counteract the effects of meat on in
the long run
don't know we should try that actually
we could do that in the lab
but uh getting to the bottom of this
what i think is going on is that
just like testosterone and growth
hormone you will get temporary
maybe not temporary um immediate health
benefits
you'll feel great you'll get more muscle
energy
but the problem is i think it's at the
expense of long-term health and
longevity
well this is actually something i worry
about
in terms of long-term effects or
the the cost in terms of longevity it's
very difficult to know
how your choices affect your longevity
because
the impact is down the line like
just because something makes me feel
good now
like eating only meat makes me feel good
now i wonder what are the costs down the
line
well think about what i i was saying
about the trade-offs between
growth and reproduction which is what a
mouse does and a whale that
grows slowly reproduces slowly lives a
long time
it's called the disposable soma theory
um kirk would just
uh propose that in the 70s what meat
probably does is put you in
the mouse category super fertile grow
fast heal fast
and then if you want to be a whale you
should restrict
meat uh and do things that promote the
preservation of
your body is it uh difficult to eat a
plant-based
diet that uh you perform well under
so uh mentally and physically just
almost i'm asking uh
almost like a anecdotal question unless
you know the science
uh well the science is still being
worked out but
from the synthesis of everything i've
read i try to
eat a diet that's definitely full of
leafy greens
uh particularly spinach is great because
it's got the iron that we need
plenty of vitamins i also
try to avoid too much fruit
and berries particularly fruit juice
definitely avoid that sugar high
spiking your sugar is not healthy in the
long run
the other thing that's interesting is we
discovered what are called what we call
xeno hormetic molecules let me unpack
that
because it's terrible name and i take
full responsibility with my friend
conrad howitz the xeno means cross
species
and hormesis is the term that what
doesn't kill you makes you live longer
and and and be healthier and so we're
getting cross
species health improvements by molecules
that plants make
and plants make these molecules when
they're also under adversity
or perceived adversity for instance uh
i understand if you want really healthy
or good oranges
you can drive nails into the the bark of
the tree before you harvest
same with wine you typically want them
to be dry before you harvest
or covered in fungus and that's because
these plants make these colorful
and xenohemetic molecules that make
themselves stress resistant turn on
their
sirtuin defenses the sir genes remember
and when we eat them we get those same
benefits that's the idea and we've
evolved to do so this isn't a
coincidence
it's my theory our theory that we want
to know when our food supplies
is under adversity because we need to
get ready for a famine
and so we hunker down and preserve our
body and by eating these colored foods
so
practically speaking if it's full of
color or if there's been some chewing by
a caterpillar caterpillar
organic grown locally in local farms
i'll eat that
versus a watery insipid uh light-colored
um lettuce that's been grown in
california so you want vegetables that
have suffered you want the david goggins
as the vegetables
that's the xenochromatic molecules i
love that tone
i'm gonna take that one with me thank
you yeah
oh i follow him on instagram is always
screaming so you want the
that he's basically uh the the
the xeno-harmonic version of a human
um i like it so these are the molecules
that are representative of
the stress that's been um
that a plant has been under yeah the
best example of that is resveratrol
which many people including myself
take as a supplement grapes or grape
vines produce that in abundance when
they're
dried out or they have too much light or
fungus
and that we've shown activates the so2
enzyme in our bodies which remember is
what extends lifespan in yeast and
slows down aging in the brain that's
beautiful yeah i tend to avoid fruit
as well so green veggies anything that's
not very sweet
so i would just say you're relatively
low like you try to avoid sugary things
as well yeah i'm fairly militant about
that um i rarely would
add sugar to anything occasionally i
would um
eat a slice of cheesecake but that would
be you know maybe once or twice a year
you have to give in occasionally but
yeah anything that's sweet i would
rather substitute something like stevia
if i need a sugar hit
what about exercise your favorite topic
is there uh is there anybody talking
about it yeah okay great is there
benefits to longevity
from exercise well no doubt that's
that's proven
um just like fasting it's pretty clear
that that works
uh for example there are studies of
cyclists
it was something like people that cycle
over 80 miles a week
have a 40 reduction in a variety of
diseases certainly heart disease
so that that's not even a question but
what's interesting is that we're
learning that
you don't need much to have a big
benefit it's an asymptotic curve
and in fact if you overdo it you
probably have reduced benefits
particularly if you start to wear out
joints that kind of thing
but just 10 minutes on a treadmill a few
times a week getting your lose your
breath get hypoxia because it's cold
seems to be very beneficial for
long-term health
um and that's the kind of exercise that
i like to do aerobic
though i do enjoy uh lifting weights so
that is what i call my exercise which
has other benefits including
maintaining hormone levels male hormone
levels
but also really why i do it is i want to
be able to
counteract the effects of sitting for
most of the day yeah and
as you get older you lose muscle mass
it's a percent or so a year
and i don't want to be frail when i'm
older and fall over and break my hip
which is which happens every 20 seconds
in this country
so maintaining that strength but also
doing the cardio for the longevity for
the avoiding the heart disease
yeah i definitely just like with fasting
have the philosophical benefit of
running long and running slow i enjoy
because it kind of clears the mind and
allows you to think
and actually listen to brown noise as i
run it really helps
remove myself from the world and just
like zoom in on particular thoughts
what is brown noise it's like white
noise but deeper so like
the white noise is like shh and then
brown noise is more like
like ocean that sounds great i might try
that yeah
yeah it's a small sweet thing probably
i'm not sure there could be signs to
this i need to look this up i've been
meaning to
but i've when i started uh
this is maybe like five years ago i
started listening brown noise when i
work
and uh the first time i listened to it
something happened to my mind
where it just went like zoomed in
to like in a way that it felt like
really weird
like how how precisely was able to sort
of
remove the distractions of the world and
really help my mind obviously like the
mind is trying to focus
and then it just enabled that process of
trying to focus
on a particular problem i don't know if
this is generalizable to others people
should definitely try it if you're
listening to
this maybe it's just my own mind but
it's funny like it made me brown noise
made me realize that there's probably
hacks out there
that work for me that i should be
constantly looking for it's almost like
um
an encouraging and motivating
of event that maybe there's other stuff
out there maybe there's other
brown noise like things out there that
truly like almost immediately make me
feel better
i don't know if it's generalizable to
others but it does seem that
it's the case that there's probably for
many others things
like that that could be discovered and
so
it's always disappointing when i find
things in life
that i wish i had found earlier like i
got lasik
eye surgery a few years ago
and the first thought i had like the
next day when i woke up is like
damn it why didn't i do this way earlier
there's other stuff
of that nature that um they're yet to be
discovered so it pays to explore
yeah though you have a different mind
you have quite a beautiful mind so i
suspect brown noise helps you
focus and because you're probably all
over the place if you don't control it
yeah exactly i mean it's something about
it it's a programmer thing i don't
the programming is a really difficult
um mental journey because you have to
keep a lot of things in mind
you have to uh so you're constantly
designing things
and you have to be extremely precise by
making those things concrete in code
you also have to look stuff up on the
internet
to sort of feed like information and
looking up stuff on the internet
internet is full of like distracting
things so you have to be really focused
in the way you look stuff
up in pulling that information in so it
requires a certain discipline and a
certain focus
that uh i've been very much exploring
how to do like
i do it really well in the morning
coffee is involved all those kinds of
things you're trying to optimize
uh keeping very positive inspired no
social media all those kinds of things
and trying to optimize for and everybody
has their own kind of
little journey that they try to
understand you get this from like
writers
when you read about the habits of
writers
like the habits they do in the morning
they usually write like two three four
hours a day and that's it
it's like they optimize that ritual and
then there's always hunters thompson
so uh
sometimes it pays off to be wild what
about
the sleep how important is sleep for
longevity
i would guess based on the evidence that
it's really important
and because we don't know for sure but
what we know from animal studies
is the following if you restrict sleep
from a rat for just two weeks it'll
develop
type 2 diabetes it's that important
so that's the main thing what we also
know is at the molecular level
that if you disrupt your
sleep wake cycle so we actually have
proteins that go up and down that
control our sleep wake
all of us most of our cells do that if
you disrupt that you'll get premature
aging and guess what the opposite is
true that as you get older
that cycle the the amplitude becomes
diminished
and this is why it's harder to get to
sleep as you get older and then
you've got all sorts of problems and i
think what's going on is this positive
feedback loop which
is is a disaster in your old age which
is um
right you're aging you can't at this
moment
totally prevent that and then it's
disrupting your sleep then you get not
enough sleep and then that's going to
accelerate your aging process
um and so it's known that that people
who are shift workers are more
susceptible
to certain age-related diseases so your
bottom line you definitely want to work
on that it's one of the reasons i have
this ring on my finger which helps me
optimize my sleep and learn
what i do the day before if it was a bad
idea and i'll stop doing that like
eating a fried chicken
i see you're still carrying the burdens
of that decision
but is yeah you know sleep is one of
those things that's making me
wonder about the variability between
humans a little bit and how
science is often focused on
like it's not often focused on high
performers in a particular way
and it's looking at the aggregate versus
the individual cases
for example like for me i don't know
what the exact hours are but
like power naps are incredible
i tend to look at the metric of stress
and happiness
and joy and try to optimize those so
decreasing stress increasing happiness
and using sleep as just one of the tools
to do that
because like hitting the five six seven
eight nine hour mark or whatever the
correct mark is
i find that to be stress inducing for me
versus
stress relieving like thinking about
that i
i feel best if i sleep sometimes for
eight hours sometimes for four hours and
then power nap
and as long as i have a stupid private
usually smile on my face
that's when i'm doing good as opposed to
getting
a perfect amount of sleep according to
whatever the
latest blog post is and i also pull
all-nighters still
i also think there's something about the
body like as long as you do it
regularly it's not as stress-inducing
like you know what
you know what it is the reason i pull
all-nighters isn't for like
i'm playing diablo 3 or something is
because i'm doing something i'm truly
passionate about well
i can also love video games but i'm
doing something i'm truly passionate
about
and it's almost like there's the jocko
willing feeling of when i'm
up at seven a.m and i haven't slept all
night
and still i'm working on it there's a
kind of a celebration of the human
spirit that i really enjoy it
like uh and that's happiness and to sort
of
then and i usually don't tell that kind
of stuff to people because
their first statement will be like you
should get more sleep
it's like no i'm doing stuff i love
you should get more love in your life
bro that's right
so but that said in aggregate when you
look at the full span of life
it's probably you should be getting
a consistent amount of sleep and it
seems like it's in that
seven eight hour range yeah but it's
similar to food
it it's the quality not the quantity
right and and when you get it
so i i look at my my data pretty often
and what makes a difference to me is not
the amount of hours but
the quality the depth and the deep sleep
is what
what'll do it so if i have a lot of
alcohol before going to sleep
and i can see my heart rate being
different but what really kills me is
that i don't
get a lot of that deep sleep and i wake
up you know barely remembering stuff
so that like you say if you're happy and
contented and you're not don't have
these
cortisol chemicals going through your
body you will more naturally get into
that deep state
and even if you just get four hours way
better than eight hours of none of that
yeah yeah that's beautiful and some of
that could be genetic for me i just
i just fall asleep like this if you want
me to fall asleep right now i can do it
it's it's no um i have no problem with
the combined with coffee i just had two
energy drinks i could probably
uh sleep so that i don't know if that's
genetics or
it's kind of um i don't know what it is
or maybe that i don't have kids that i'm
single so i don't have uh
i'm almost listening to some kind of
biological signal versus
societal signal on when i'm supposed to
go to sleep so i just
go to sleep whenever i feel like going
to sleep well that's because you're
self-employed so most people don't have
that luxury
but we're lucky the two of us that we
can make our own hours yeah
um but yeah it's super important and
those people who have
the shift work i mean they they really
need to to
change the way that works because
they're literally killing those people
is there something you can say about the
the mind and stress
uh in terms of effect on longevity
sort of um because i don't know if you
think about it this way but
when you talk about the biological
machine it's always these mechanisms
that don't are not necessarily directly
connected to the brain
or the operation of the brain like
what's the role about
stress and happiness and uh
yeah the sort of higher cognitive things
going on in the brain
on longevity right well that's a great
point that the brain is is the center
for longevity actually
we we do know that first start when when
i'm stressed
i can see mentally stressed then i can
see it in my body
heart rate hormones it's clear you know
that's no
true surprise so you've got to work on
your brain first and foremost if you are
totally freaked out agitated uh
all the time you will live shorter i'm
certain of it you know i keep
fish i'm a big
aquarium guy and you can see the
difference between the the fish that's
having a good time and dominant
and one that gets picked on yeah it just
looks like crap
you don't want to be that the little
fish getting picked on if you can help
it
so i used to be extremely stressed as a
kid i was a perfectionist
very shy always worried about being a
failure
if i didn't get an a plus you know i was
crying in my bedroom that kind of sad
existence i got into my 20s then in my
30s and realized
that's not the way to live so i've
worked very hard to get to this point
where
i almost never get stressed never
there's nothing that
i've never gotten angry in my lab i've
got 20 kids sometimes it's like a
most of the time it's like a
kindergarten um i
haven't lost my temper i very calm but
that's intentional
um and i don't worry about stuff
millions of dollars
billions of dollars at stake sometimes
keep it cool it's only life we're all
headed to the same place anyway
don't worry about it um but the the to
answer your question i think
in a better way if you manipulate the
brain of an animal
i'll give you an example if we turn on
this cert gene that i mentioned sir one
we a good friend of mine that wash you
shiny my did this
they upregulate the operate of that gene
just in the neurons of the animal
it lived longer so that's sufficient to
extend lifespan
we also know that you can manipulate the
part of the brain
called the hypothalamus which leaches a
lot of chemicals into the body
and proteins most of which we don't know
yet
but just changing the inflammation of
that little organ
or part of the brain is sufficient to
make animals live longer as well
so get your brain in order first before
you tackle anything else i would say
so you kind of mention this with the
inside tracker
there's a ability to take blood
measurement
and then infer from that
a bunch of different things about your
body how you can improve
how you can improve the longevity and
you've also mentioned
saliva and more efficient ways
to uh to get data uh
what does that involve what's the future
of data collection look like yeah for
the human biological system
right well yeah the the issue with with
blood is you need someone to take it
it's
it i mean or you prick your finger which
hurts yes so you gotta have something
better so i think what the future
looks like is that you'll spit onto a
little piece of paper and stick it in a
machine and it'll it'll do that for you
but we're not there yet so the
intermediate um
future that that i'm building right now
is that you would take a
swab of the inside of your mouth which
is the easiest way to take cells out of
your body
and just ship them off okay so called a
buckle swab
um i think we we became very used to
that right right now
because of covert people don't like
going to the doctor as much they don't
like going out they just want to have
home tests
and so that i think is the next 10 years
where you'll get a kit in the mail
you'll swab your cheek stick it back in
an envelope send it off and
you know a week later you have either a
doctor's report
or a health recommendation and what can
you get
off a cheek swab well you can get
anything you can get hormones stress
levels
stress hormones blood glucose levels you
can also tell your age
reasonably accurately doing that
actually quite accurately and those
clocks
cannot just tell you how you're doing
over time
but can be used to give you
recommendations to slow that process
down
because some people sometimes are 10
years older biologically than their
actual
chronic chronological age i mean
why does it matter how many times the
earth's gone around the sun seriously
who cares about birthdays
it's how long your body's clock has been
ticking and how fast
so i could take a cheek swab from you
today lex take it back to my lab
and we then by tomorrow tell you how old
you are biologically
based on what we call the epigenetic
clock
and you might be freaked out you might
be happy but either way we can
advise you on how to improve the
trajectory because we know that smoking
increases the speed of that clock
we also know that fasting and people who
eat the right foods
have a slower clock without that
knowledge you're flying blind
but i like the idea of a swab because
it's it's just so easy we've a lot of us
have done something like that for covert
tests it's not even i've been doing a
non-stop a rapid antigen test
so let me say that particular one
rapid antigen test they've been a source
of frustration for me because like
everybody should be doing it
it's so easy we've also been working in
my lab on democratizing these tests to
bring them down from a few hundred bucks
to a dollar
so just to clarify you're talking about
not research you talk about like company
stuff
like actual facing things i i well
right the research on bringing the price
down has occurred in my lab at harvard
and then that intellectual property is
being licensed and has been licensed out
to a company
yeah that that will be uh
consumer-facing so anybody
for a small amount of money can do this
well you got subscriber number one
obsessed i think that's a beautiful
beautiful idea so somebody who
maybe i would have been more hesitant
about it until a covid
uh but home tests are super easy i
almost wanted to share that data with
the world
like in some way not not the entirety of
the data but like
some visualization of like how i'm doing
like
it's almost like uh like you know when
you share if you had like
a long run or something like that i wish
i could share
because it inspires others and then you
can have a conversation about like
well what are the hacks that you've
tried and have a conversation about like
how to improve lifestyle and those kinds
of things
that's grounded in data that's exactly
that's what's that's what's going to
happen now
everything's anonymous of course we
talked about security there
but once it's anonymized you can then
plot these numbers and i've plotted my
epigenetic age versus hundreds of other
people who have taken this
test now and i can tell you where i fit
relative to others in terms of my
biological age
and i'm happy to share that with you all
because it's pretty low
you can choose to share it of course not
everyone wants to share that
but when you go to the doctor first of
all your doctor doesn't
does treat you as though you're an
average person and none of us are
average there's no such thing
but second of all we never know how
we're doing relative to others because
we all
most of us we we don't share our
information so we might have this number
and that number
but do you know that your numbers are
good for your age or not
you have no idea no even your doctor
probably doesn't even know
so this this graph that i'm talking
about is the beginning of a world where
you can say how am i doing
i'm a you know for the two of us we're
white and we're male
and we're this age and we do this
are we good are we doing the right
things or the wrong things do we need to
fix certain things
and this is what the future is it's
forget about
just experimenting and not knowing the
result i mean who doesn't experiment and
doesn't look at the data
no one it makes no sense so we're going
to enter a world where we have a
dashboard in our body
the swabs the blood tests the biosensors
where
our doctors can look at that but we can
also look at it
and they can recommend you know go to
this restaurant down the road they've
got this great meal
it's high in whatever you need today
because you're lacking vitamin d and
vitamin k2 go for it
ridiculous question or perhaps not if
you look maybe 50 years from now or 100
years from now a person born then
what do you think is a good goal in
terms of how long a person would live
like what is the maximum longevity that
we can achieve through the methods
that we have today of uh or are
developing some of the things we've been
talking about
and in terms of genetics in terms of
biology
what's is there a number
right uh well so it changes all the time
because technology's changing so quickly
i keep revising the number
upward uh but i would say that if you do
the right things during your life and
start at an early age let's say 25 we
don't want malnutrition starvation
that's not what i'm talking about
but in your 20s start eating the kind of
diets that i talked about
skipping meals in animals that gives you
an extra 20
to 30 percent we don't know if that's
true for humans and that would
you know even five percent more would be
a good a big deal for the planet
i think that we should all aim to at
least reach a century
um i i'm i'm a little bit behind i was
born too early to benefit
the most from all of this discovery
those of you who are in your twenties
you should definitely aim to reach a
hundred i don't see why not
consider this is really important the
average life span of a human
that looks after themselves and but
doesn't pay attention
is about 80 okay japan that's the
average age for a male
bit higher if you do the right things
in your life which is eat
healthy food don't overeat don't become
obese do a bit of exercise get good
sleep and don't stress
that gives you on average 14 extra years
that gets you to 94.
so getting to 100 if you just focus on
what i'm talking about
it's not a big deal so what's the
maximum well we know that
one human made it to 122 and a number of
them make it into their
teens i think that's also the next level
of
of uh of where we can get to with the
types of technologies that i'm talking
about
medicines like i mentioned rapamycin
there's one called metformin which is
the diabetes drug
which i take that in combination with
these lifestyle changes should get us
beyond a hundred
how long can we ultimately live well
there's no maximum limit to human
lifespan why can a whale live 300 years
but we cannot
we're basically the same structure we
just need to learn from them
so anyone who says oh you max max out at
x
i think is is full of it there's nothing
that i've seen that says biological
organisms have to die there are trees
that live for thousands of years
and their biochemistry is pretty close
to ours
what do you think it means to live for a
very long time let's say if it's 200
years we're talking about or a thousand
years
there's some some sense you could argue
that there is
immortal organisms already living on
earth like there's bacteria so
there's certain there's certain living
organisms
that in some fundamental way do not
die because they keep replicating their
genetic information
they keep like cloning themselves
is is it the same human
if we can somehow persist the human mind
like copy clone certain aspects and just
keep replacing
body parts um do you think that's
another way to achieve immortality
to achieve of a prolonged sort of
increased longevity is
to replace the parts that break easily
and keep
because actually from your theory of um
aging as a degradation of information
it's an information theory view of
aging like what is what is the key
information that makes a human
can we persist that information and just
replace
the the trivial parts uh yeah i mean the
short answer is yes we're already
replacing body parts but
what makes us human is our brain
everything else is is sub-optimal
except our brain the
ability to replace actual neurons is
really hard
right i think it might be easy to upload
rather than
replace neurons because they're so tight
it's such a network
and just perturbing the system you know
it's
it's uh it's stretching this cat you
you change everything once you get in
there the problem is um
well i guess the solution let me go to
the solution that's more interesting
what we're learning is that if you
reverse the age of nerve cells
they look it looks like they get their
memories back
right so the memories are not lost
they're just that the cells don't know
how to
interpret them and function correctly
and this is one of
the things we're starting in my lab if
you take an old mouse that has learned
something when it was young
but forgotten does it get that back and
all evidence points to that being true
so i'd rather go in and rejuvenate the
brain as it sits rather than replace
individual cells which would be really
hard
what do you think about like efforts
like neurolink
which basically you mentioned uploading
are trying to figure out so creating
brain computer interfaces
they're trying to figure out how to
communicate with the brain
but one of the features that is trying
to record the human brain
more and more accurately do you have
hope for that
to um of course there's uh it will lead
to us better understanding
from a neuroscience perspective the
human mind but do you have
hope for it increasing longevity in
terms of
how it's used i think that it can help
with certain diseases
uh but i see at least within our
lifetime that's the best use of it is to
be able to replace parts of the body
that
are not functioning such as the the
retina and other parts the visual cortex
back here
that that's going to be doable in terms
of longevity
maybe we could put something on the
hypothalamus and
start secreting those hormones and get
that back
ultimately i think it the best way to
preserve the brain
uh is going to be to uh
record it but also i think it's going to
require death unfortunately
to then do very detailed scans even
if you have enough time and money atomic
microscopy and rebuild the brain from
scratch
rebuild from scratch yeah we are
living more and more in the digital
world
i wonder if if the scanning is good
enough for the critical things in terms
of
memories in terms of the particular
quirks of your cognitive processes
they're not they're not yeah we're not
we're not close yes but
we've made quite a bit of progress so
it's uh
if you're um if you're an exponential
type of person
yeah well let's dream a little here yes
the way it would work
that i could see it working is so you
take a single cell slice through your
your dead brain and we can now the
problem the problem with the engineering
aspect is that the engineering is the
physical aspect of the brain is is
not even half the problem the problem is
which genes are
switched on and off this experience that
we're having here is
is altering certain genes in neurons
that will be preserved hopefully for for
a number of decades
but you cannot see that with a
microscope easily
but there are technologies invented
actually just down the hall
in the building i'm at george church
invented away his lab invented a way
to look at which genes are switched on
and off
not only in a single cell which any lab
can do these days
but in situ where it's situated in the
brain so you can say okay
this nerve cell had these genes switched
on and they switched off
we can recreate that but just scanning
the brain and looking how the nerves are
touching each other is not going to do
it
wow okay so you have to scan the full
biology
the full details and look at the
epigenome and the apogenome too yeah
which genes are on and off
it's just easier to reset the epigenome
and get them to work like they
just use we're doing that now use the
hardware already have just figure out
how to uh
make that hardware last longer right
ultimately information will be lost
even genetic information degrades slowly
through mutations so we
immortality is not achievable through
that means though i think we could
potentially reset the body hundreds of
times and live for thousands of years
okay so we talked about biology
let's forgive me but let's talk about
philosophy for just a brief moment
so somebody i've enjoyed reading ernest
becker wrote the denial of death there's
also
martin heidegger there's a bunch of
philosophers who
claim that most people live life in
denial of death
sort of we
don't fully internalize the idea that
we're going to die
the
because if we did as as they say there
will be a kind of
terror of um i mean
a deep fear of death the fact that we
don't know what's
like we almost don't know what to do
with non-existence with disappearing
like our
the way we draw meaning from life seems
to be grounded in the fact that we exist
and that we some point will not exist is
terrifying and so
we live in an illusion that we're not
going to die and we run from that terror
that's what ernest beckham would say do
you think there's any truth to that
oh i know there's truth to that i
experience it every day when i talk to
people
we have to live that way although
unfortunately
i can't but for most people it's
extremely stressing distressing to think
about their own
mortality we think about it occasionally
and if we really thought about it every
day
we'd probably be brought to tears how
much we not just miss ourselves but miss
our family our friends we are
all living life forms have evolved to to
not want to die
and when i mean one biochemically
genetically physically
that yeast cell the cells that i studied
at mit
they were fighting for their lives they
didn't think
but our brain has evolved the same
survival aspect
of course we don't want to die but the
problem for us unfortunately
it's a curse and a blessing is that
we're now conscious we know
that we're going to die most species
that have ever existed don't
that's a burden that's a curse and so
what i think's happened is
we've evolved certainly to want to live
for a long time perhaps
never want to die but the thought about
dying is so traumatic
that there is an innate part of our
brains and it's probably
genetically wired to not think about it
i really think that's part of being
human and it because
you know think about tribes that
obsessed with longevity every day and
that were going to die they probably
didn't make much technological
progress because they were just crying
in their hearts every day or you know on
the savannah
so i really think that we've evolved to
naturally
deny aging and it's one of the problems
that i face in my career
and you know when i speak publicly and
on social media
is that it's shocking people don't want
to think about their age but i think
it's getting better
i think my book has helped these tests
that we're developing should help people
understand it's not a problem to think
about your long-term health
in fact if you don't you're going to
reach 80 and really regret it
and the other side of it so again ernest
becker but also
victor franklin recommended highly man
search for meeting
uh bernard williams he's a moral
philosopher
they kind of argue that this knowledge
of death even if we often
don't contemplate it we do at times
and the very the what you call the curse
which i agree with you it's a
it's a curse and a blessing that we're
able to contemplate our own mortality
that gives meaning to life so death
gives meaning to life
is what viktor frankl's argues i would
probably argue the same there's
something about the scarcity
of life and contemplating that that
makes each moment
that much sweeter is there something to
that
i think it's individual in my case it's
completely wrong
i appreciate you saying that i don't get
joy out of
every day because i think i'm going to
die yeah i get joy out of every day
because every day is joyous and i make
it that way
and even if i would if i thought i was
going to live forever
i would still be enjoying this moment
just as much
and i bet you would too well that's uh
i think about that a lot i i think
it's very difficult to know i'm almost
afraid
that i wouldn't enjoy it as much if i
was immortal i'm almost afraid to want
to be immortal or
to live longer because
it perhaps is a kind of justification
for me to
accept that i'm going to die is saying
like oh if i was immortal i wouldn't be
able to enjoy life as much as i do
but it's very possible that i wouldn't
enjoy just as much
of course enjoying life whether you're
mortal or not
takes work like it it requires you to
have
the right kind of freedom of mind you
can discover
you can focus your mind on the ugliness
of life
there's plenty of ugly things in this
world and you can focus on them you can
complain
whenever like you know if it's raining
outside
you can you can focus on the fact that
you have shelter and you enjoy the the
hell
out of it or you can enjoy running in
the rain when it's warm and like
the the beauty of nature just being one
with nature or you can just complain
this fucking weather again in boston
and there you see they're always raining
or freezing damn it and like
uh the the same the same thing with like
wi-fi going out on airplanes
like you can either complain about like
stupid wi-fi and on jetblue or something
or you could say like how incredible it
is that i can fly through the sky and in
a matter of hours be anywhere else in
the world
and then it could also on occasion watch
uh like check email and even watch
movies through this
while connecting through satellites that
are flying to space so it's a matter of
perspective and perhaps
there's an extra level of work required
when you're immortal
because it's easier when you're immortal
or live longer to
uh to be lazy to delay stuff but if
you're not
you can still derive the same amount of
joy it's possible
it's possible it's definitely possible
in my life
i i went from being the nothing's
working to
every day is great to wake up to and i i
think even if you
live i think you're gonna live forever
you can you can enjoy every day
what i do is everything's relative we
can compare ourselves to our neighbor
who has more money
or to the flight that should have had
wi-fi or
which is what i do i'm still six years
old remember what a six-year-old does
says look i can when i tell my fingers
to form a fist they actually do that
that's really cool
that's how i live my life you know i'm i
can pick up on your desk here this metal
object it's a metal cube
about an inch by an inch by an inch and
i i tell myself not
not about cubes but about inanimate
objects
probably once a day i'll say i'm a
living thing i can think i can move i
can eat i am
full of energy and there's that leaf or
this cube here that will never be alive
that's what i look at and compare myself
to
and for as long as i live if it's
forever of course it won't be but
even if it was forever the relative to
this lump of metal on this table here
we are wondrous things in the universe
and probably the most wondrous things in
the universe yeah we're able to
deeply appreciate the leaf or the cube
and deeply appreciate ourselves which is
uh
it can be a curse but it's mostly a gift
especially when you're such a beautiful
poem
now i'm six i'm as clever as clever so i
think i'll be six
now forever and ever that's a good thing
to aspire to
your uh your grandmother was on to
something david this is uh
incredible conversation i'm a huge fan
of your work so
thank you for wasting your valuable time
with me today i really really appreciate
it this was awesome thank you for having
me on lex appreciate it
thanks for listening to this
conversation with david sinclair and
thank you to
on it clear national instruments
simply safe and linode check them out in
the description to support this podcast
and now let me leave you some words from
arthur shorpenhauer
all truth passes through three stages
first it is ridiculed second it is
violently opposed
third it is accepted as being
self-evident
thank you for listening and hope to see
you next time
you